Sunday, November 04, 2007

Breaking into the brain   posted by p-ter @ 11/04/2007 11:25:00 AM

Nature has a news piece on vastly improved models for psychology-related phenotypes in model organisms. It's worth a read, keeping in mind James Watson's claim from last year that "the past century was the coming together of chemistry and biology, and this century will be the coming together of psychology and biology".

The story highlights the progress being made in studying the brain the way other organs have been studied for years. And right after I read it, I saw a couple papers that hammer the story home.

First, Molecular Adaptations Underlying Susceptibility and Resistance to Social Defeat in Brain Reward Regions, which shows that genetically identical mice can be divided into two groups based on how they respond to social defeat (from the paper: "An episode of social defeat is accomplished by forcing a mouse to intrude into the space territorialized by a larger mouse of a more aggressive genetic strain, leading to an agonistic encounter that ultimately results in intruder subordination.") and identifies particular molecules whose expression levels differentiate the two, mostly involved in a specific signaling pathway that goes through a protein encoded by BNDF (brain-derived neurotrophic factor).

How could genetically identical mouse strains react so differently to stress? The authors don't really know, offering only this:
Such examples of phenotypic variability in inbred mice have always been attributed to environmental influences that are difficult to control and measure, such as variations in prenatal and postnatal development and early dominance hierarchies ([Peaston and Whitelaw, 2006] and [Wong et al., 2005]). However, experiments performed on inbred mice raised in strictly defined environments have shown that up to 80% of random variability in quantitative traits (e.g., body weight) are unrelated to genetic and environmental influences (Gartner, 1990). This third component to natural variation is thought to maintain Gaussian distributions of biological variables independent of environmental influences and sequence constraints and is now attributed to chromatin remodeling events such as histone acetylation or methylation.
So perhaps it's just random chance?

In humans, however, there is genetic variation in the genes these authors identify, including a non-synonymous (Met->Val) polymorphism in Bndf that affects the expression level of the gene. The authors are able to test this polymorphism in their framework:
We show here that while Val/Val and Met/Met mice showed comparable behavior on baseline measures of emotionality, Met/Met mice displayed a striking Unsusceptible [to depression following social defeat] phenotype in the social defeat paradigm, which was associated with a ~50% reduction in levels of BDNF protein
It's quite possible, then, that this polymorphism plays an important role in how humans respond to certain social situations, though this remains to be seen.

The other paper that caught my eye was on the results of performing brain MRIs on people from the general population. I never would have thought to check if individuals had had random small strokes, but that's what they find:
Asymptomatic brain infarcts were present in 145 persons (7.2%). Among findings other than infarcts, cerebral aneurysms (1.8%) and benign primary tumors (1.6%), mainly meningiomas, were the most frequent. The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence.
So around 10% of individuals over 50 are walking around with some sort of brain damage. I suppose there are a couple ways to respond to that information-- either you adapt your view of what a normal brain is, or you become suspicious of anyone above a certain age.

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